Actionable Genotypes and Life Span in Iceland

To the Editor: Jensson et al. (Nov. 9 issue)(1) report the results of a population-based genotyping study involving 57,933 Icelanders, focusing on the analysis of pathogenic variants in 73 genes for which effective medical interventions are available (i.e., actionable genotypes). The most notable finding was the considerably shorter survival among persons who were heterozygous for pathogenic variants in cancer-susceptibility genes. A strikingly inferior outcome was observed in male participants heterozygous for the pathogenic Icelandic p.Asn257LysfsTer17 founder variant in BRCA2, among whom survival was 4.6 years shorter than among noncarriers. This variant was reported in 1996,(2) and soon after, it was . . .